The long-term goal of this research is to help define and characterize the cellular inflammatory responses that are seen in human immediate hypersensitivity states. The nature of the cellular infiltrate and the kinetics of the appearance of such cells into tissue sites will be further characterized, with particular emphasis on the skin. The mechanisms involved in the attraction and/or retention of cells at the tissue sites will be explored by: 1) relationship of the intensity of accumulation of different cell types with the degree of clinical and skin test reactivity of the subject; 2) determination of antecedent changes in mast cells at the sites; 3) in vivo and in vitro chemotactic studies with fluid phase components of the tissue inflammatory reaction; 4) comparative studies in which the injection of antigen follows local pre-treatment with agents which should block the release of some mediators following interaction of antigen with reagin-sensitized cells. Additional studies will focus on chemotactic activity which we have found in the serum during induced immediate hypersensitivity reaction in the human respiratory tract. The kinetics of this activity will be determined with relationship to the provocative challenge and the clinical/pulmonary function states of the patient population. The physico-chemical characteristics of chemotactically active serum fractions and mechanisms of liberation of this activity will be determined and compared with chemotactic factors obtained from chamber fluid and from in vitro challenge of sensitized basophils and lung tissue. The nature of the responding cell population will be further defined, by in vitro and in vivo measurements.